Histone deletion mutants challenge the
molecular clock hypothesis

Early in the development of the molecular clock hypothesis,
it was discovered that not all proteins "ticked" at
the same rate. When compared across a range of species, the fibrinopeptides,
for instance, were much "faster clocks" (i.e., having
a higher rate of amino acid substitution) than the very conservative,
"slowly ticking" histones. These differences, writes
Michael Behe (Chemistry, Lehigh University), required a modification
to the clock hypothesis: the postulate of functional constraints.
Thus, for example, histone H4 would diverge less rapidly than
fibrinopeptides if a larger percentage of H4 amino acid residues
were critical for the function of the molecule. (p. 374)

The problem with the notion of functional constraint, Behe
argues, is an absence of experimental support:

Although plausible, it has long been realized that no direct
experimental evidence has been obtained 'showing rigorously that
histone function is especially senstive to amino acid substitution
or that fibrinopeptide function is especially insensitive to
amino acid substitution.' (p. 374)

"Recent experiments," writes Behe, "now indicate
that the key assumption of functional constraints may not be valid."

Since the histones are so highly conserved -- "the H4
sequence of the green pea differs from that of mammals by only
two conservative substitutions in 102 residues" -- one might
expect that "few, if any, substitutions could be tolerated
in the H4 sequence" (p. 374). However, experiments (reported
in detail by Behe) have shown that large parts of the histone
molecule may be deleted without significantly affecting the viability
of the organism (in this instance, yeast) -- results which, Behe
argues, should trouble defenders of the molecular clock hypothesis:

[The experimental] results pose a profound dilemma for
the molecular clock hypothesis: although the theory needs the
postulate of functional constraints to explain the different
degrees of divergence in different protein classes, how can one
speak of 'functional constraints' in histones when large portions
of H2A, H2B and H4 are dispensable for yeast viability? And if
functional constraints do not govern the accumulation of mutations
in histones, how can they be invoked with any confi-dence for
other proteins? (p. 375)

The resolution of the dilemma, Behe contends, must "as
far as possible be grounded in quantitative, reproducible experiments,
rather than in simple correlations with time that are its current
basis" (p. 375). Otherwise, he concludes:

[T]he time-sequence correlation may end up as a curiosity,
like the tracking of stock market prices with hemline heights,
where correlation does not imply a causal relationship.